The objective of this research is to study the mechanism of signal transduction from the insulin receptor to two membrane transporters: the (Na,K)ATPase and a Na channel. The methods of protein chemistry and molecular biology will be used. The structure of the insulin receptor will be studied to determine the importance of the dimeric structure of the receptor for signal transduction; the interaction of G proteins with the receptor and the dependence of this interaction on the dimeric structure of the receptor are also questions of interest. The region in the primary structure of the alpha2 isoform of the (Na,K)ATPase that is necessary for regulation of the pump by insulin will be investigated by making hybrid alpha1/alpha2 polypeptides and by studying the molecules that interact with this region of the (Na,K)ATPase. The insulin dependent Na channel identified in skeletal muscle will be isolated, characterized, and the gene for the channel cloned and expressed; the relationship of this channel to other Na channels will be of particular interest.